The naturally occurring photosensitizer, hypericin, with its high quantum yield of singlet oxygen photogeneration was studied for its ability to differentiate between glioblastoma cells and fetal rat neurons using fluorescence microscopy. Eight human glioma cell lines and twelve primary human glioma cell cultures were compared to human astrocytes and cerebellar granule neurons after incubation with 20 microM hypericin for 5-120 min. Photobleaching effects have been studied by exposing the cell lines to 100 msec of excitation light (510-550 wavelength). Mainly, perinuclear hypericin staining was detected. Neurons can be differentiated from glioblastoma cell lines and astrocytes by a lower fluorescence intensity (Tukey-Kramer HSD test, p < 0.0001). Therefore, hypericin seems to be a promising substance for the photodynamic therapy of malignant brain tumors.